Early Viral Infections in CF Infants Associated with Lung Inflammation, Bacterial Infections, Study Finds

Early viral infections cause inflammation and bacterial infections in the lower airway of the lungs of infants with cystic fibrosis (CF), according to a study.

The prospective study, “Early respiratory viral infections in infants with cystic fibrosis,” was published in the Journal of Cystic Fibrosis.

Although bacterial infections are considered the primary cause of inflammation of the airways in patients with CF, viral infections also play a key role as a lung pathogen. Studies have shown that infants with CF can develop lung diseases such as bronchiectasis in the absence of bacteria.

Previous studies have shown that antiviral treatments can reduce hospitalization rates in infants with CF caused by certain viral infections. Also, viral infections are linked with infections by common bacteria, including Pseudomonas aeruginosa, the leading cause of CF-associated lung infections.

Now, a team of researchers investigated the link among early viral infections, CF-associated respiratory symptoms, pulmonary inflammation, and bacterial infections in infants with CF.

In total, 70 infants with CF (mean age 3.1 years), from four centers in the U.S. (20 participants) and Australia (50 participants), were enrolled in the study based on newborn screening. All the infants had sweat chloride levels above 60 mEq/L (indicating a high likelihood of CF), or two pathogenic cystic fibrosis transmembrane conductance regulator (CFTR) mutations (the underlying cause of CF).

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Participants attended study visits at one- to three-month intervals. Nasopharyngeal swabs (gathering samples from the nose and throat to assess upper respiratory tract infections) were collected during the study visits, or at home by the parents when participants showed disease symptoms.

Researchers found that the majority of the participants (76%) showed at least one nasal swab positive for viral infection during the study period. The human rhinovirus, which causes the common cold, was the virus most frequently detected (66%), followed by parainfluenza virus (19%), and coronavirus (16%).

The team also found that 26% of the participants experienced respiratory symptoms, with coughing (15% of symptomatic participants) and nasal congestion (17% of symptomatic participants) the most common. These symptoms increased the likelihood of finding viral infections in participants’ lungs.

However, researchers found no differences in hospitalization rates between infants with no reported viral infections and infants with reported viral infections.

The team used bronchoscopy with bronchoalveolar lavage to collect lung samples and diagnose lung disease. According to the analyses, participants with past viral infections had higher counts of neutrophils (a type of immune cells) in the lungs, compared with participants with no recorded viral infection (230,000 and 110,000 cells/mL of epithelial lining fluid, respectively).

Past virus infection was also associated with bacterial growth (77% compared with 45% in the no-virus infection group), and CF-related bacteria isolated from bronchoalveolar lavage (32% compared with 5% in the no-virus infection group).

The presence of bacterial pathogens in the lungs was further associated with increased pulmonary inflammation, seen by higher levels of neutrophil elastase (an enzyme secreted by neutrophils) and IL-8 (a protein secreted by some immune cells).

Regarding treatment, researchers observed differences in antibiotic-based strategies between the U.S. and Australia. For example, preventive antibiotic treatment against Staphylococci is standard in Australia, while in the U.S. infants received more antibiotic courses upon new respiratory symptoms than in Australia.

Researchers saw that 52 percent of the participants receiving systemic antibiotic treatment (56% in the U.S. and 47% in Australia) experienced some virus infection. Also, infants who had received preventive antibiotic treatment showed higher levels of inflammation markers (neutrophil elastase and TNF-α), compared with those not receiving the treatment.

“There are several lines of evidence to support a mechanistic link between viral infections and lower airway bacterial colonization,” the researchers stated, suggesting that “viruses clearly play a role in the airway, the most significant of which may be their interaction with immune defense and bacteria.”

Overall, the team concluded that while viral infection rates do not differ between infants with CF and healthy controls, as reported by previous studies, early viral infections in infants with CF are associated with inflammation and bacterial infections of the lower airway. The researchers emphasized that more research is needed to understand the link among viral infections, bacterial infections, and antibiotics use in infants with CF.